DeCure for Hepatic veno-occlusive disease-immunodeficiency syndrome
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for hepatic veno-occlusive disease-immunodeficiency syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHepatic veno-occlusive disease-immunodeficiency syndrome maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedZidovudineApproved drug
Structures already discussed alongside hepatic veno-occlusive disease-immunodeficiency syndrome in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Thymidine phosphorylase from E.coli — Zidovudine has a real, experimentally solved structure in complex with this target (PDB 4LHM, 1.52 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet azzdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4LHM · 1.52 Å · ligand Zidovudine (AZZ). Experimental structure, not a prediction.
What the evidence adds up to
Hepatic veno-occlusive disease with immunodeficiency (VODI) is an autosomal recessive disorder caused by mutations in the SP110 gene, which encodes a PML nuclear body protein. A 2013 review of eight kindred members with VODI identified a new SP110 mutation. Five of those patients underwent haematopoietic stem cell transplantation, and three were successfully corrected. The authors concluded that transplantation can be successful if applied early with appropriate conditioning, but the sample is small and the previous literature had reported a high rate of complications.
A 2022 thesis confirmed that the SP110 gene is responsible for VODI by homozygosity mapping and DNA sequencing, and showed absence of the Sp110 protein in patient B cells by immunofluorescence. The same thesis attempted to test whether SP110 alleles influence susceptibility to hepatic veno-occlusive disease in bone marrow transplant patients from the Fred Hutchinson Cancer Center, Seattle. A single nucleotide polymorphism association study found initial evidence for an association, but the study lacked sufficient power after correction for multiple testing. A separate SNP association study in a New South Wales cohort of Mantoux-positive South East Asian migrants detected evidence that SP110 alleles might be associated with progression of Mycobacterium tuberculosis infection, but again the limited cohort size precluded definitive findings.
A 2014 case report described a Pakistani patient with a homozygous novel SP110 variant who presented at three months of age with opportunistic infections and later developed liver failure. The authors stated that earlier diagnosis and treatment improve prognosis, but provided no survival or response-rate data for that patient. No controlled trial of any drug for VODI has been reported in these abstracts.
What is still missing is a sufficiently powered genetic association study to confirm SP110’s role in transplant-related veno-occlusive disease, any prospective trial of haematopoietic stem cell transplantation with standardised conditioning, and a clear definition of which patient subgroups (age, mutation type, liver function at baseline) benefit most. No drug therapy is mentioned in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pediatric Allergy and Immunology · 2013 · 19 citations · open access
The role of hematopoietic stem cell transplantation in <scp>SP</scp>110 associated veno‐occlusive disease with immunodeficiency syndrome
AbstractBACKGROUND: Veno-occlusive disease with immunodeficiency (VODI) is an autosomal recessive disorder of combined immunodeficiency (CID) and hepatic injury. Hematopoietic stem cell transplantation (HSCT) - the only definitive treatment for CID - appeared to have a high rate of complications in a previous report. In this study, we describe a new group of patients with VODI highlighting further clinical and immunologic aspects of this disease and re-evaluating the effectiveness of HSCT for the treatment of this disorder. PATIENTS AND METHODS: Review of clinical data, immunologic features, molecular studies, treatment, and final outcome of eight kindred members with VODI. RESULTS: The patients described had clinical and immunologic findings consistent with VODI. The molecular studies revealed a new mutation in the SP110 gene. HSCT was carried out in five patients and was successful in three. CONCLUSIONS: The diagnosis of VODI should be considered in all patients regardless of ethnicity with a severe combined immunodeficiency (SCID)-like presentation, especially with a normal mitogen response, or with signs of hepatic injury. VODI is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of disease using appropriate conditioning.
UNSWorks (University of New South Wales, Sydney, Australia) · 2022 · 0 citations · open access
The genetic basis of veno-occlusive disease with immunodeficiency syndrome
AbstractThis thesis addresses the genetic basis of a rare autosomal recessive primary immunodeficiency disorder with the characteristic additional feature of venoocclusive disease of the liver (VODI). The interest in this condition was stimulated both by the potential to identify the genetic basis of a rare immunodeficiency and the opportunity to gain an insight into the biological basis of hepatic veno-occlusive disease, a poorly understood condition that is encountered most frequently in Australia as a consequence of bone marrow transplantation. The gene responsible for VODI was identified by homozygosity mapping and DNA sequence analysis of positional candidates and was shown to be the PML Nuclear Body expressed protein Sp110. This is the first time a PML Nuclear Body protein has been shown to be involved in immunodeficiency disorder. Subsequent immunofluorescence studies of affected patient cell lines showed absence of Sp110 in patient B cells. The role of SP110 alleles in the susceptibility of bone marrow transplant patients to hepatic veno-occlusive disease was investigated using a cohort of patients from the Fred Hutchinson Cancer Center, Seattle. A SNP association study identified initial evidence for an association, but the study lacked sufficient power after correction for multiple testing. Contemporaneously, Dr Igor Kramnik published a report that the murine homologue of Sp110, Ifi75 (also termed Ipr1) was deleted in mice that were supersusceptible to infection with Mycobacterium tuberculosis. A further SNP association study was therefore performed utilising a NSW cohort of Mantouxpositive South East Asian migrants, which detected evidence that alleles of SP110 may be associated with progression of M. tuberculosis infection. Again, the limited size of this cohort precluded definitive findings.
Case Reports in Pediatrics · 2014 · 0 citations · open access
MENGUNGKAP PEMAHAMAN INFORMASI AKUNTANSI DARI SUDUT PANDANG KEPALA SEKOLAH SMA NEGERI X : Studi Fenomenologi Pada SMA Negeri X
AbstractFamilial hepatic veno-occlusive disease with immunodeficiency (VODI, OMIM: 235550) is a rare form of combined immune deficiency (CID) that presents in the first few months of life with failure to thrive, recurrent infections, opportunistic infections along with liver impairment. Herein, we are describing a Pakistani patient with a homozygous novel variant in the <i>SP110</i> gene, presenting with classical phenotypic manifestations of VODI. He presented at the age of 3 months with opportunistic infections and later developed liver failure. <i>Conclusion</i>. Hepatic veno-occlusive disease with immunodeficiency is a rare cause of immunodeficiency, and this is the first case report from the Middle East in a patient of Pakistani origin. It is important to have a high suspicion for this disease, in patients presenting early life with a picture of CID and deranged liver function, as the earlier the diagnosis and treatment, the better the prognosis.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
